Inhibitory mechanisms in the prefrontal-cortex differentially mediate Putamen activity during valence-based learning.

Learning from appetitive and aversive stimuli is important for survival. It involves interactions between the prefrontal cortex and subcortical structures, with inhibition playing a crucial role. However, direct evidence for this in humans is limited. Here, we overcome the difficulty of measuring inhibition in the human brain and find that GABA, the main inhibitory neurotransmitter, affects how the dACC interacts with subcortical structures during appetitive and aversive learning differently. We used 7T magnetic resonance spectroscopy (MRS) to track GABA levels in the dACC alongside whole-brain fMRI scans while participants engaged in appetitive and aversive learning tasks. During appetitive learning, dACC GABA levels were negatively correlated with learning performance and BOLD activity measured from the dACC and the Putamen. While under aversive learning, dACC GABA concentration negatively correlated with the functional connectivity between the dACC and the Putamen. Our results show that inhibition in the dACC mediates appetitive and aversive learning in humans through distinct mechanisms.